Short- and long-term effects of leucine and branched-chain amino acid supplementation of a protein- and energy-reduced diet on muscle protein metabolism in neonatal pigs

Abstract

The objective of this study was to determine if enteral leucine or branched-chain amino acid (BCAA) supplementation increases muscle protein synthesis in neonates who consume less than their protein and energy requirements, and whether this increase is mediated via the upregulation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway or the decrease in muscle protein degradation signaling. Neonatal pigs were fed milk replacement diets containing reduced energy and protein (R), R supplemented with BCAA (RBCAA), R supplemented with leucine (RL), or complete protein and energy (CON) at 4-h intervals for 9 (n = 24) or 21 days (n = 22). On days 9 and 21, post-prandial plasma amino acids and insulin were measured at intervals for 4 h; muscle protein synthesis rate and activation of mTOR-related proteins were determined at 120 min post-feeding in muscle. For all parameters measured, the effects of diet were not different between day 9 or day 21. Compared to CON and R, plasma leucine and BCAA were higher (P ≤ 0.01) in RL- and RBCAA-fed pigs, respectively. Body weight gain, protein synthesis, and activation of S6 kinase (S6K1), 4E-binding protein (4EBP1), and eukaryotic initiation factor 4 complex (eIF4E·eIF4G) were decreased in RBCAA, RL, and R relative to CON (P < 0.01). RBCAA and RL upregulated (P ≤ 0.01) S6K1, 4EBP1, and eIF4E·eIF4G compared to R. In conclusion, when protein and energy are restricted, both leucine and BCAA supplementation increase mTOR activation, but do not enhance skeletal muscle protein synthesis and muscle growth in neonatal pigs.

Intermittent leucine pulses during continuous feeding alters novel components involved in skeletal muscle growth of neonatal pigs

“…Conversely, valine and isoleucine-related metabolites such as N-acetylisoleucine and glycylisoleucine decreased in response to leucine pulses, while the corresponding αketoacids 3-methyl-2-oxobutyrate and 3-methyl-2-oxovalerate increased, though not significantly (Online Resource 1), in LEU compared with CON piglets. These results are consistent with our earlier findings that the post-prandial levels of valine and isoleucine are impacted by both parenteral (Boutry et al 2013(Boutry et al , 2016 and enteral leucine supplementation (Manjarín et al, 2016(Manjarín et al, , 2018, likely due to the leucine-induced upregulation of the activity of the branched chain (BC)-keto acid dehydrogenase enzymatic complex, which results in the catabolism of all BCAAs (Tannous et al 1963;Harper et al 1970).…”

Regulation of Muscle Growth in Early Postnatal Life in a Swine Model

“…Thus, when newborn pigs are fed a proteinrestricted diet, Leu supplementation alone has a limited capacity to restore lean growth (40). Moreover, when newborn pigs are fed an energy-and protein-restricted diet, Leu supplementation does not improve body weight gain although mTORC1 activation is sustained, suggesting that low energy intake supersedes an anabolic effect of Leu (41,42).…”

Review: Nutritional regulation of muscle growth in neonatal swine

“…However, there is no evidence of changes in acetyl-CoA carboxylase ( ACC ) (an indicator protein of AMPK activity) abundance or phosphorylation due to amino acids, insulin, or age. Additionally, results from previous work show no change in AMPK phosphorylation following amino acid supplementation, indicating a low likelihood that AMPK plays a vital role in amino acid-driven mTORC1 activation in neonatal muscle ( Rudar et al, 2021a ; Manjarín et al, 2020 ; Suryawan and Davis, 2018 ; Manjarín et al, 2018 ; Boutry et al, 2013 ).…”